Bottom Line:
Normal liver has little type I collagen and no detectable myofibroblasts, but myofibroblasts appear early in experimental and clinical liver injury.In fact, the origin of myofibroblasts may be different for different types of chronic liver diseases, such as cholestatic liver disease or hepatotoxic liver disease.This review will examine our current understanding of the liver myofibroblast.

Affiliation: University of California, San Diego, School of Medicine, San Diego, CA, USA.

ABSTRACTMost chronic liver diseases of all etiologies result in progressive liver fibrosis. Myofibroblasts produce the extracellular matrix, including type I collagen, which constitutes the fibrous scar in liver fibrosis. Normal liver has little type I collagen and no detectable myofibroblasts, but myofibroblasts appear early in experimental and clinical liver injury. The origin of the myofibroblast in liver fibrosis is still unresolved. The possibilities include activation of endogenous mesenchymal cells including fibroblasts and hepatic stellate cells, recruitment from the bone marrow, and transformation of epithelial or endothelial cells to myofibroblasts. In fact, the origin of myofibroblasts may be different for different types of chronic liver diseases, such as cholestatic liver disease or hepatotoxic liver disease. This review will examine our current understanding of the liver myofibroblast.

Mentions:
There are at least three potential sources of myofibroblasts in the liver (see Figure 1). The resident mesenchymal cells, consisting of the quiescent hepatic stellate cell and the tissue fibroblasts, can potentially become myofibroblasts. These cells are characterized by CD45-, CD34-, desmin+, glial fibrillar associated protein (GFAP)+, and thy-1+. Recent studies have proposed hepatocytes, cholangiocytes, and endothelial cells can become myofibroblast through epithelial or endothelial mesenchymal transition (EMT). These cells include CD45-, albumin+ (i.e. hepatocytes), CD45-, CK19+ (i.e. cholangiocytes), or Tie2+ (endothelial cells). Finally, bone-marrow derived cells, consisting of fibrocytes and circulating mesenchymal cells, can be recruited to the injured liver to become myofibroblasts. These cells are CD45+ (fibrocytes), CD45+/- (circulating mesenchymal cells), collagen type I +, CD11d+, and MHC class II+.

Bottom Line:
Normal liver has little type I collagen and no detectable myofibroblasts, but myofibroblasts appear early in experimental and clinical liver injury.In fact, the origin of myofibroblasts may be different for different types of chronic liver diseases, such as cholestatic liver disease or hepatotoxic liver disease.This review will examine our current understanding of the liver myofibroblast.

Affiliation:
University of California, San Diego, School of Medicine, San Diego, CA, USA.

ABSTRACTMost chronic liver diseases of all etiologies result in progressive liver fibrosis. Myofibroblasts produce the extracellular matrix, including type I collagen, which constitutes the fibrous scar in liver fibrosis. Normal liver has little type I collagen and no detectable myofibroblasts, but myofibroblasts appear early in experimental and clinical liver injury. The origin of the myofibroblast in liver fibrosis is still unresolved. The possibilities include activation of endogenous mesenchymal cells including fibroblasts and hepatic stellate cells, recruitment from the bone marrow, and transformation of epithelial or endothelial cells to myofibroblasts. In fact, the origin of myofibroblasts may be different for different types of chronic liver diseases, such as cholestatic liver disease or hepatotoxic liver disease. This review will examine our current understanding of the liver myofibroblast.